The Lipid Mass Spectrometry Core is to provide support for all PPG Projects with state-of-the-art technology to quantify sphingosine-1-phosphate (SIP) and related signaling sphingolipids in tissues, biological fluids and endothelial cells. The task of reliable and sensitive quantitation of sphingolipid mediators and other small molecules derived from biological samples under normal and pathological conditions, in the presence of complex mixture of closely related compounds, is best resolved by tandem mass spectrometry in conjunction with liquid chromatography (LC/MS/MS). The Lipid Mass Spectrometry Core is equipped with AB Sciex 5500 Qtrap triple quadrupole-ion trap hybrid mass spectrometer and we have already developed reliable and sensitive electrospray ionization-tandem mass spectrometry-based methods for quntitation of major signaling sphingolipids such as SIP, ceramides and sphingoid bases as well as their synthetic analogs FTY720, its phosphate and phosphonate derivatives. Cellular and tissue samples generated within all 4 projects of the program will be centrally analyzed to provide uniformity and quality control to quantitative sphingolipid analyses within the Program Project. This approach will help integrate projects since SIP/ceramide changes are increasingly implicated in endotoxinand radiation-induced lung injury (Project 1), are potentially linked to the dynamic changes of SIP receptors during endotoxin- and radiation-induced lung injury (Project 2 and 4), are instrumental in mediating FTY720- phosphonate based therapies (Project 3), and might be biomarkers for the development of acute lung injury (Project 2) and radiation-induced pneumonitis (Project 4). SIP-ceramide levels can be manipulated via sphingosine kinases, SIP lyase (Project 1) and by FTY720P or its analogs (Project 3). The Mass Spectrometry Core is also integrated with other Core facilities and research programs of the University of Chicago with major emphasis on quantitation of lipid mediators involved in signal transduction, cardiovascular and pulmonary diseases. In summary. Mass Spectrometry Core will be central in providing data on signaling sphingolipidom changes as a result of acute lung injury and radiation-induced pneumonitis.